Differential regulation of IL-8 by IL-1beta and TNFalpha in hyaline membrane disease.
Mechanisms that regulate cytokine-mediated inflammation in the lungs of preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lavage samples were obtained from preterm newborns with hyaline membrane disease over a 28-day period. Bronchoalveolar lavage cell cytokine relationships were evaluated and the differential regulation of IL-8 by IL-1beta and TNFalpha was studied in a short-term culture system. In vivo, IL-8 and IL-1beta protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1beta antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNFalpha antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1beta and anti-TNFalpha antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-1beta antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1beta, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1beta and TNFalpha regulate IL-8 expression in the lungs of preterm infants.
Kwong
K Y
KY
Department of Pediatrics, Women's & Children's Hospital, Los Angeles County, University of Southern California Medical Center, 90033, USA.
Jones
C A
CA
Cayabyab
R
R
Lecart
C
C
Stotts
C L
CL
Randhawa
I
I
Ramanathan
R
R
Khuu
N
N
Minoo
P
P
deLemos
R A
RA
D019138:Antibodies, Blocking / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006819:Hyaline Membrane Disease / Q000276:immunology*; D007231:Infant, Newborn; D007234:Infant, Premature; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D019138:Antibodies, Blocking; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha